Solvent‐Free Mechanocatalytic Reduction of Nitro Compounds with Hydrogen Gas and its Application in the Synthesis of Drugs and their Intermediates

A solvent‐free mechanochemical method for the catalytic hydrogenation of nitro compounds is reported, requiring only the substrate, low catalyst loading, and molecular hydrogen. The approach avoids the use of additional base additives or solvents for liquid‐assisted grinding. The transformation proceeds under mild conditions using palladium on carbon and hydrogen gas in pressurizable stainless steel jars operated in a planetary ball mill. A variety of functionalized nitro compounds are converted to the corresponding anilines and amines in good to excellent yields. The method displays chemoselectivity, tolerating functional groups such as halogens, benzylic ketones, and nitriles. In addition, scale‐up to multigram quantities is achieved, and an analysis of trace metal impurities from abrasion revealed only minor concentrations, all below the limits established by ICH guidelines. The protocol's practicality is demonstrated by synthesizing intermediates and active ingredients used in pharmaceuticals and agrochemicals. To quantify the sustainability of the protocol, green metrics are calculated and compared with those of other mechanochemical and solution‐phase nitro compound reduction methods.